The Neural Basis of Spontaneous Action

自发行动的神经基础

• 批准号: 10056793
• 负责人: Michael H Dickinson
• 金额: $ 45.79万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056793
• 关键词: ARNT gene; Ablation; Anatomy; Animals; Antibodies; Architecture; Atmosphere; Behavior; Behavioral; Biophysics; Brain; Cell model; Cell physiology; Cells; Chronic; Collection; Cues; Denmark; Development; Diagnosis; Drosophila genus; Exhibits; Flying body movement; Foundations; Frequencies; Functional Imaging; Generations; Genetic; Genetic Models; Gilles de la Tourette syndrome; Goals; Grant; Human; Huntington Disease; Image; Impairment; Individual; Interneurons; Label; Lateral; Lead; Learning; Lighting; Lobe; Maps; Measures; Modeling; Molecular; Nervous system structure; Neurons; Neuropil; Noise; Parkinson Disease; Pattern; Physiological; Physiology; Process; Psychophysics; Reagent; Research; Role; Saccades; Sensory; Side; Stains; Structure; Synaptic Transmission; System; Techniques; Testing; The Sun; Time; Work; design; experimental study; fly; in vivo; innovation; member; motor learning; nervous system disorder; optogenetics; patch clamp; polarized light; relating to nervous system; screening; sensory stimulus; statistics; synaptotagmin; tool; two-photon

Project Summary Although behavior is largely structured by sensory cues, animals also benefit from random actions. Stochastic actions and variability are important for many behaviors including motor learning, search, and predator evasion. Furthermore, understanding the cellular basis of stochasticity may be pertinent to many neurological disorders involving the inability to either suppress or generate involuntary actions, including Tourette's syndrome, Huntington's chorea, and Parkinson's disease. Despite its importance, the mechanisms underlying the generation of random actions at the molecular, cellular, or network levels are poorly understood. Understanding spontaneous processes in the nervous system will benefit from research in a tractable genetic model in which both its functional role and mechanistic basis could be studied vertically across phenomenological levels. Recently, a genetically identified neuron has been identified cell (called DNa04) in the fruit fly, Drosophila that serves as a command neuron for rapid spontaneous turns, called saccades. This is a rare case of a single genetically identified neuron whose activity is necessary and sufficient for stochastic actions. Although it is already possible to record from this command neuron using 2-photon imaging and in vivo patch clamp, the primary goal of this proposal is to identify members of the upstream network that is responsible for generating its stochastic activity. Toward these goals, Specific Aim 1 of this proposal will focus on screening a collection of ~20 selective split-GAL4 lines labeling interneurons in the Lateral Accessory Lobe (LAL), the upstream neuropil region that is thought responsible for generating the spontaneous activity in the DNa04 cell. We will perform 2- photon functional imaging in intact flying flies to record from LAL interneurons and use genetic tracing techniques including trans-Tango to map the connectivity within the network. In Specific Aim 2 we will explore the function of individual cells in generating the pattern of spontaneous activity by manipulating cell physiology using a variety approaches including optogenetic activation and silencing. Specific Aim 3 will focus on psychophysical experiments aimed at quantifying and modeling the influence of sensory stimuli that modulate the frequency of spontaneous saccades. By mapping the network and experimentally manipulating the physiology of its member cells, we will lay the foundation for developing a quantitative model of the cellular basis of spontaneous actions in the brain.

项目摘要 虽然行为主要是由感官线索构成的，但动物也从随机行为中受益。随机 动作和可变性对许多行为都很重要，包括运动学习、搜索和捕食者逃避。 此外，理解随机性的细胞基础可能与许多神经系统疾病有关 包括无法抑制或产生无意识的行为，包括图雷特综合征， 亨廷顿舞蹈病和帕金森病。尽管其重要性， 在分子、细胞或网络水平上随机行为的产生知之甚少。理解 神经系统中的自发过程将受益于对易处理的遗传模型的研究， 它的功能作用和机制基础都可以在现象学的各个层面上进行纵向研究。 最近，在果蝇（Drosophila）中发现了一种基因鉴定的神经元细胞（称为DNa 04）， 充当快速自发转向的命令神经元，称为扫视。这是一个罕见的情况下，一个单一的 遗传上确定的神经元，其活动对于随机行为是必要和充分的。虽然 已经有可能使用双光子成像和体内膜片钳从该命令神经元记录， 该提案的主要目标是确定负责生成的上游网络的成员 它的随机活动。为了实现这些目标，本提案的具体目标1将侧重于筛选一批 ~20条选择性分裂GAL 4线标记外侧副叶（LAL）中的中间神经元， 该区域被认为负责在DNA 04细胞中产生自发活动。我们将执行2- 在完整的苍蝇中进行光子功能成像，以记录LAL中间神经元并使用遗传追踪技术 包括trans-Tango来映射网络内的连接。在具体目标2中，我们将探索功能 通过使用各种不同的方法操纵细胞生理学， 包括光遗传学激活和沉默的方法。具体目标3将侧重于心理物理 实验旨在量化和模拟感官刺激的影响，调节的频率， 自发性扫视通过绘制网络图并实验性地操纵其成员的生理机能 细胞，我们将奠定基础，发展一个定量模型的细胞基础的自发行动 在大脑中。